This program project has supported our efforts concerning the differentiation and the molecular genetics of human leukemias. In this renewal we propose to continue such efforts and have broadened the scope of the program. We intend to investigate the molecular genetics of specific chromosome rearrangements, predominantly translocations and inversions, in B cell, T cell and myeloid cell neoplasms. These rearrangements will be studied at the cytogenetic and at the molecular level. The genes involved in these rearrangements will be cloned, characterized and sequenced. Their expression will be studied in different hematopoietic cells and in non-hematopoietic tissues. Their protein products will also be purified and characterized and their expression in normal and neoplastic tissues investigated. In addition, we propose to insert the open reading frames of the activated proto-oncogenes in retrovirus vectors to determine their ability to cause neoplastic transformation in mice and rats. Finally we intend to introduce the activated oncogenes into fertilized mouse eggs to study their expression during cell differentiation and mouse development. Thus, this multidisciplinary approach to the study of human hemotopoietic neoplasms should result in an understanding of the molecular events leading to neoplastic transformation of hematopoietic cells in man.